Osteoarthritis is a heterogeneous disorder that is increasingly prevalent largely due to aging and obesity, resulting in a major disease burden worldwide. Knowledge about the underlying aetiology has improved, with increased understanding of the role of genetic factors, the microbiome, and existence of different pain mechanisms. However, this knowledge has not yet been translated into new treatment options. New evidence has questioned the efficacy of recommended treatments, such as therapeutic exercise programmes and the focus on weight loss, but managing obesity and maintaining activity remain important for the prevention and management of osteoarthritis. Approaches should consider individual and cultural preferences and resource availability to increase patient and community engagement, and optimise outcomes worldwide. Most of the focus has been on established osteoarthritis where management is primarily directed at relieving symptoms. The search for the much needed effective treatments that improve both symptoms and structure, often referred to as disease-modifying osteoarthritic drugs, is ongoing. Promising data indicate that targeting inflammation is effective in hand osteoarthritis.

Spatial repellent products are used for prevention of insect bites, and a body of evidence exists on spatial repellent entomological efficacy. A new option for vector control, spatial repellent products are designed to release active ingredient into the air for disruption of human-vector contact thereby reducing human exposure to mosquito-borne pathogens. Clinical trials have shown spatial repellent epidemiological efficacy against Aedes-borne viruses but inconclusive outcomes against malaria. We aimed to show and quantify the protective efficacy of spatial repellents in reducing malaria infection incidence in Busia County, Kenya.

Interleukin-23 inhibition is effective in treating ulcerative colitis. Guselkumab is a dual-acting, human IgG1, interleukin-23p19 subunit inhibitor that potently neutralises interleukin-23 and can bind to CD64. We aimed to evaluate the efficacy and safety of guselkumab as induction and maintenance therapy in patients with ulcerative colitis.

Health systems experience difficult trade-offs when paying for new drugs. In England, funding recommendations by the National Institute for Health and Care Excellence (NICE) for new drugs might generate health gains, but inevitably result in forgone health as the funds cannot be used for alternative treatments and services. We aimed to evaluate the population-health impact of NICE recommendations for new drugs during 2000-20.

Trials of endovascular therapy for basilar artery occlusion, including vertebral occlusion extending into the basilar artery, have shown inconsistent results. We aimed to pool data to estimate safety and efficacy and to explore the benefit across pre-specified subgroups through individual patient data meta-analysis.

In this Review, we examine the concurrent outbreaks of mpox in Africa, focusing on clade 1a, the newly emerged clade 1b, and clade 2b lineage A, and how they differ from the 2022 global outbreak caused by clade 2b lineage B.1. Historically, clades 1a and 2a have caused sporadic, small outbreaks in central and west Africa, respectively, primarily through zoonotic transmission. Clade 2b first caused an outbreak in Nigeria in 2017, and later spread globally via sexual contact in 2022. In August, 2024, WHO declared a global health emergency due to the newly identified clade 1b outbreak in eastern Democratic Republic of the Congo. This outbreak has now expanded to several other countries and is spreading through direct and sexual contact in urban centres and refugee camps. Clades, route of exposure, infectious dose, and host immune response are the main factors influencing clinical presentation of mpox. For clades 1a and 2a, zoonotic transmission plays an important role, whereas for clades 1b and 2b, the spread occurs through sustained human-to-human transmission without zoonotic exposure. For both clades 1a and 2a, lesions have a generalised centrifugal distribution, whereas for clade 2b they are mainly localised to the anogenital area. For clade 1b, data are still emerging, but current cases show a mix of localised lesions and centrifugal distribution. The severity of the disease is higher for clade 1a (case fatality rate up to 12%) compared with other clades (case fatality rates 0-3·6%). Diagnostic challenges include false negative results for clade 1b with existing PCR assays and poor testing access in remote areas. Tecovirimat, the primary antiviral during the 2022 outbreak, has shown reduced effectiveness against clade 1a in preliminary study results, whereas its efficacy against other clades is still under investigation. The modified vaccinia Ankara-Bavarian Nordic vaccine has been shown to be up to 90% effective against clade 2b after two doses and is safe for children, although its effectiveness drops to 20% when used as post-exposure prophylaxis. Given the evolving nature of the monkeypox virus, ongoing research and strong public health responses are key to managing potential future outbreaks.

The six global nutrition targets (GNTs) related to low birthweight, exclusive breastfeeding, child growth (ie, wasting, stunting, and overweight), and anaemia among females of reproductive age were chosen by the World Health Assembly in 2012 as key indicators of maternal and child health, but there has yet to be a comprehensive report on progress for the period 2012 to 2021. We aimed to evaluate levels, trends, and observed-to-expected progress in prevalence and attributable burden from 2012 to 2021, with prevalence projections to 2050, in 204 countries and territories.

Chronic pancreatitis is a progressive fibroinflammatory disease primarily caused by a complex interplay of environmental and genetic risk factors. It might result in pancreatic exocrine and endocrine insufficiency, chronic pain, reduced quality of life, and increased mortality. The diagnosis is based on the presence of typical symptoms and multiple morphological manifestations of the pancreas, including pancreatic duct stones and strictures, parenchymal calcifications, and pseudocysts. Management of chronic pancreatitis consists of prevention and treatment of complications, requiring a multidisciplinary approach focusing on lifestyle modifications, exocrine insufficiency, nutritional status, bone health, endocrine insufficiency, pain management, and psychological care. To optimise clinical outcomes, screening for complications and evaluation of treatment efficacy are indicated in all patients with chronic pancreatitis.

This Health Policy examines the relationship between child cash benefits and child health, with the goal of informing future policy development in the USA. As of 2024, more than 140 countries have adopted large-scale, government-funded child cash transfer programmes. High-income countries more often adopt universal or near universal programmes, while lower-income countries often impose means tests or condition benefits on specific behaviours. Evidence on the adoption of child cash benefits from a broad set of nations finds that they can improve a range of child health outcomes, with the most robust evidence of health benefits occurring when delivered to children younger than 5 years and during the prenatal period. During the 2021 expanded Child Tax Credit (CTC), the USA briefly joined other high-income countries by introducing a near universal, unconditional child cash benefit, which led to a historic decline in child poverty. Although the expanded CTC expired, state and local governments and communities have continued to advocate for and implement policies like it. On the basis of this success and building on global evidence, the USA should adopt a permanent child cash benefit consistent with other high-income countries and the 2021 expanded CTC. Nations further developing their cash benefits should also give special attention to the prenatal and infant period.

As the beginning of the next US presidential administration approaches, the USA faces a series of complex challenges that threaten the health of the American people and the effectiveness and sustainability of their health and health-care systems. Taking office in January, 2025, the next administration will need to address myriad systems-level and public health challenges, including the long-term health impacts of COVID-19 and threat of future pandemics, negative effects of climate change on health, unaffordability and inefficiencies in health care, and resulting and long-standing disparities in health-care access and health outcomes. Without decisive policy action, population health is likely to stagnate or even deteriorate. We present five priority areas to guide US federal strategy in 2025 and beyond: improve public health and address health and social inequities; catalyse transformation towards a more effective, equitable health system; address crucial health issues such as climate change; advance artificial intelligence for health and health care; and strengthen responsible science and innovation. To achieve these goals, we suggest policy action items for federal stakeholders and emphasise the importance of social determinants of health, cross-sector collaboration, population health perspectives, and transformative partnerships. By prioritising these strategic imperatives, the incoming administration can set a plan towards a healthier, more resilient future for all Americans.

The capacity to anticipate future health issues is important for both policy makers and practitioners in the USA, as such insights can facilitate effective planning, investment, and implementation strategies. Forecasting trends in disease and injury burden is not only crucial for policy makers but also garners substantial interest from the general populace and leads to a better-informed public. Through the integration of new data sources, the refinement of methodologies, and the inclusion of additional causes, we have improved our previous forecasting efforts within the scope of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to produce forecasts at the state and national levels for the USA under various possible scenarios.

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides a comprehensive assessment of health and risk factor trends at global, regional, national, and subnational levels. This study aims to examine the burden of diseases, injuries, and risk factors in the USA and highlight the disparities in health outcomes across different states.

Patients with severe aortic stenosis present frequently (∼50%) with concomitant obstructive coronary artery disease. Current guidelines recommend combined surgical aortic valve replacement (SAVR) and coronary artery bypass grafting (CABG) as the preferred treatment. Transcatheter aortic valve implantation (TAVI) and fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) represent a valid treatment alternative. We aimed to test the non-inferiority of FFR-guided PCI plus TAVI versus SAVR plus CABG in patients with severe aortic stenosis and complex coronary artery disease.

Allogeneic haematopoietic stem-cell transplantation is the standard treatment for bone marrow failure (BMF) in patients with Fanconi anaemia, but transplantation-associated complications such as an increased incidence of subsequent cancer are frequent. The aim of this study was to evaluate the safety and efficacy of the infusion of autologous gene-corrected haematopoietic stem cells as an alternative therapy for these patients.

Sudden cardiac arrest and death occur among competitive and recreational athletes across the entire spectrum of age, sex, and level of competition. These events are tragic, potentially preventable, and represent a global public health concern. Currently, the precise incidence of sudden cardiac arrest and death among all athletes is uncertain due to the lack of both mandatory case reporting and the infrastructure to process all cases that occur within the general population. Disparities in outcomes between Black and White athletes also exist without explanation. Causes of sudden cardiac arrest and death are age-dependent, with genetic heart conditions and unexplained cases (ie, normal autopsy) predominant among younger athletes, and coronary artery disease accounting for most cases among veteran Masters athletes. Determining best practices for prevention of primary sudden cardiac arrest and death, including preparticipation screening, remains controversial. However, secondary prevention grounded in an emergency action plan incontrovertibly represents a fundamental aspect of comprehensive cardiac care for all athletes.

Hand eczema is a highly prevalent skin disease and one of the most common work-related disorders. In up to two-thirds of individuals affected by hand eczema, the disease becomes chronic and results in substantial personal and occupational disability. Manifestations of chronic hand eczema vary in severity and appearance over time, and people with eczema typically experience itch, pain, and a burning sensation. The pathophysiology of chronic hand eczema is multifactorial. Major risk factors are current or past atopic dermatitis and excessive or prolonged exposure to irritants or allergens. Based on the suspected main causes, chronic hand eczema is commonly classified into irritant, allergic, and atopic hand eczema. Diagnosis and assessment can be complex, and management is often challenging. Strategies include structured education, avoidance of trigger factors, primary to tertiary prevention, topical anti-inflammatory treatment with glucocorticosteroids, calcineurin inhibitors, or januskinase inhibitors, phototherapy, systemic retinoids, and off-label use of immunosuppressive drugs. Topical and systemic immunomodulatory therapies approved for atopic dermatitis could be used in severe atopic hand eczema and some of them are under clinical development for chronic hand eczema. Additional research is needed to better understand chronic hand eczema subtypes and underlying mechanisms, and the comparative effectiveness and safety of therapies. This Review combines established knowledge with ongoing changes in our understanding of the disease and their implications for prevention, management, and future research.

Landscape fire-sourced (LFS) air pollution is an increasing public health concern in the context of climate change. However, little is known about the attributable global, regional, and national mortality burden related to LFS air pollution.

Nearly two decades ago, the Eight Americas study offered a novel lens for examining health inequities in the USA by partitioning the US population into eight groups based on geography, race, urbanicity, income per capita, and homicide rate. That study found gaps of 12·8 years for females and 15·4 years for males in life expectancy in 2001 across these eight groups. In this study, we aimed to update and expand the original Eight Americas study, examining trends in life expectancy from 2000 to 2021 for ten Americas (analogues to the original eight, plus two additional groups comprising the US Latino population), by year, sex, and age group.

Although death in old age is unavoidable, premature death-defined here as death before age 70 years-is not. To assess whether halving premature mortality by 2050 is feasible, we examined the large variation in premature death rates before age 70 years and trends over the past 50 years (1970-2019), covering ten world regions and the 30 most-populous nations. This analysis was undertaken in conjunction with the third report of The Lancet Commission on Investing in Health: Global Health 2050: the path to halving premature death by mid-century.

Mirikizumab, a humanised monoclonal antibody that inhibits IL-23p19, is effective in moderate-to-severe ulcerative colitis. We aimed to evaluate the efficacy and safety of mirikizumab in patients with moderately-to-severely active Crohn's disease.